A comprehensive investigation of GH-somatomedin mechanisms which regulate growth will be continued. The structural characterization of rSm-basic peptide will be completed. Monoclonal antibodies will be raised against the intact molecule and its major cleavage fragments. An IGF-II-like molecule of rat serum will be purified and compared to its human counterpart. The feedback control of hypothalamic regulation of GH secretion will be studied by incubating rat hypothalami with rGH, rSm (basic peptide) and rIGF-II-like peptide. The release of somatostatin will be measured by RIA. Release of GRH will be measured in the conditioned medium by means of primary rat pituitary cell cultures after the neutralization of somatostatin with antibody. Methods for the isolation of the intact Sm-binding protein complex will be improved. The smaller 38 K binding protein will also be isolated. The carbohydrate and amino acid composition of these binding components will be determined. The SmC/IGF-I binding constants of these purified binding components will be determined. The ultracentrifugal sedimentation of these binding components will be compared to sedimentaion of bound somatomedin in native serum. GH RRA will be imporved by use of membranes prepared from IM-9 lymphocytes. Methods for characterizing GH receptors in human fat and erythrogenic precursors will be developed. The relationship between IGF-I and IGF-II in patients with tumor hypoglycemia will be studied to explain the suppression of IGF-I and increase in IGF-II which we have found in this condition. The methods of GH and somatomedin peptide measurement and detection of receptors will be applied to clinical disorders of human growth.